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Query: UMLS:C0751781 (NOD)
 6,696 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of MHC class II molecules on beta-cells of the pancreatic islet has been proposed to play a role in the genesis of insulin-dependent diabetes mellitus in the NOD mouse. We investigated this by immunofluorescent double labeling of islet cells with anti-MHC and anti-CD45 to identify cells of hematopoietic origin. MHC class I expression increased with age on CD45- islet cells. MHC class II expression was not observed on CD45- islet cells at any age; the only cells in the islet that were MHC class II positive were also CD45+. This indicates that all MHC class II-positive cells in the islet are lymphoid cells that infiltrate the islet, whereas the islet endocrine cells express no MHC class II molecules. However, an increase in MHC class I expression occurred on beta-cells, and this may play a role in immunopathogenesis.
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PMID:Exclusive expression of MHC class II proteins on CD45+ cells in pancreatic islets of NOD mice. 182 81

NOD mice spontaneously develop organ-specific autoimmunity and are widely used as a model for diabetes. NOD mice also exhibit some features of non-organ specific autoimmune rheumatic disease such as thymocytotoxic and anti-nuclear autoantibodies and they develop haemolytic anaemia in senescence. A single dose of 2.6 x 10(7) heat-killed Bacillus Calmette-Guerin (BCG) i.v. in 8-week-old NOD mice prevented diabetes but precipitated a syndrome similar to systemic lupus erythematosus (SLE), in which treated mice rapidly developed haemolytic anaemia, high titre anti-DNA and anti-Sm antinuclear autoantibodies, perivascular lymphocytic infiltration in the kidneys and glomerular immune complex deposition. Here, we examined the mechanism of action by which BCG precipitated rheumatic autoimmune disease in NOD mice. Two weeks after injection, reticuloendothelial cell function was dramatically increased in BCG-treated NOD mice. By 4 weeks, treated mice had a three- to four-fold increase in Mac-1+ and class-II+, B220-negative splenocytes and in vitro antigen-presentation capacity was enhanced two- to four-fold. In vivo responses to SRBC confirmed enhancement of DTH 4 weeks after BCG injection, consistent with an adjuvant-like activity.
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PMID:Mycobacteria precipitate autoimmune rheumatic disease in NOD mice via an adjuvant-like activity. 800 75

Flow cytometry was used to track the in vivo migration of PKH26-labeled donor spleen cells from diabetic NOD mice that were injected into non-diabetic recipient NOD mice. Flow cytometric analysis of recipient mouse tissues revealed that the donor cells were present in the peripheral blood, spleen and lymph nodes 24 h following injection and could still be detected after 28 days. PKH26(+) cells were also detectable in the pancreas 7 days after injection. Phenotypic analysis of the PKH26(+) cells that migrated into these target organs and tissues showed that the major cell population detected was Thy1.2(+) T-lymphocytes, predominantly the Thy1.2(+)/L3T4(+) subpopulation, but Thy1.2(+)/Lyt2(+) cells as well as B220(+) cells (B lymphocytes) were also present.
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PMID:Tracking of murine spleen cells in vivo: detection of PKH26-labeled cells in the pancreas of non-obese diabetic (NOD) mice. 815 88

Most female NOD mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) after the 4th month of age. We have recently reported that infection of 2-month-old NOD mice with Mycobacterium avium prevents IDDM expression in these mice. We have searched here for changes in splenic lymphocytes that are associated with the effect of M. avium vaccination. Three experimental groups of female NOD mice were studied: (i) animals infected with 10B viable M. avium bacteria (mice that become protected from IDDM); (ii) mice inoculated with 10B heat-killed (HK) M. avium bacilli, and (iii) untreated age-matched NOD mice. Similar treatments were given to mice of the NON strain which are related to NOD mice but do not develop IDDM. Flow cytometry was used to compare M. avium-infected, HK M. avium inoculated and untreated NOD and NON mice with regard to subpopulations of splenic lymphocytes bearing the surface antigens CD3, CD4, CD8, IgM and B220. We found that M. avium infection of NOD mice caused a sustained enhancement in T cells that was due to an early and transient increase in CD8+ T cells (detected at day 7 of infection). This was followed by marked augmentation in the number of CD4+ T cells at days 14 and 30. There was also elevation in B220+ B cells at days 14 and 30, and of IgM+ B cells at day 30 of infection. Inoculation of NOD mice with HK mycobacteria, which did not prevent IDDM, failed to produce significant changes in the number of T and B cells. No significant enhancement in T and B cells was observed in NON mice that were injected with either viable or HK M. avium bacilli. In NOD mice that reached 16 months of age because of being protected from IDDM (due to the M. avium infection) there was an increase in B220+ B cells. We conclude that: (i) M. avium-induced protection of NOD mice from diabetes depends on the viability of the bacteria; (ii) the protective effect of the infection is associated with an early and marked increase in helper T cells and with a smaller elevation in B cells; (iii) elevation in B cells, but not in T cells, is associated with long term mycobacteria-induced protection of NOD mice from IDDM.
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PMID:Changes in B and T lymphocytes associated with mycobacteria-induced protection of NOD mice from diabetes. 886 25

In vivo expansion and multilineage outgrowth of human immature hematopoietic cell subsets from umbilical cord blood (UCB) were studied by transplantation into hereditary immunodeficient (SCID) mice. The mice were preconditioned with Cl2MDP-liposomes to deplete macrophages and 3.5 Gy total body irradiation (TBI). As measured by immunophenotyping, this procedure resulted in high levels of human CD45(+) cells in SCID mouse bone marrow (BM) 5 weeks after transplantation, similar to the levels of human cells observed in NOD/SCID mice preconditioned with TBI. Grafts containing approximately 10(7) unfractionated cells, approximately 10(5) purified CD34+ cells, or 5 x 10(3) purified CD34+CD38- cells yielded equivalent numbers of human CD45+ cells in the SCID mouse BM, which contained human CD34+ cells, monocytes, granulocytes, erythroid cells, and B lymphocytes at different stages of maturation. Low numbers of human GpA+ erythroid cells and CD41+ platelets were observed in the peripheral blood of engrafted mice. CD34+CD38+ cells (5 x 10(4)/mouse) failed to engraft, whereas CD34- cells (10(7)/mouse) displayed only low levels of chimerism, mainly due to mature T lymphocytes. Transplantation of graded numbers of UCB cells resulted in a proportional increase of the percentages of CD45+ and CD34+ cells produced in SCID mouse BM. In contrast, the number of immature, CD34+CD38- cells produced in vivo showed a second-order relation to CD34+ graft size, and mice engrafted with purified CD34+CD38- grafts produced 10-fold fewer CD34+ cells without detectable CD34+CD38- cells than mice transplanted with equivalent numbers of unfractionated or purified CD34+ cells. These results indicate that SCID repopulating CD34+CD38- cells require CD34+CD38+ accessory cell support for survival and expansion of immature cells, but not for production of mature multilineage progeny in SCID mouse BM. These accessory cells are present in the purified, nonrepopulating CD34+CD38+ subset as was directly proven by the ability of this fraction to restore the maintenance and expansion of immature CD34+CD38- cells in vivo when cotransplanted with purified CD34+CD38- grafts. The possibility to distinguish between maintenance and outgrowth of immature repopulating cells in SCID mice will facilitate further studies on the regulatory functions of accessory cells, growth factors, and other stimuli. Such information will be essential to design efficient stem cell expansion procedures for clinical use.
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PMID:Transplantation of human umbilical cord blood cells in macrophage-depleted SCID mice: evidence for accessory cell involvement in expansion of immature CD34+CD38- cells. 949 Jun 79

In vitro studies have provided little consensus on the kinetic abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOD/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene. One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site. Similar short-term kinetics were observed using 51Cr-labeled cells. The first signs of engraftment for BV173, AP, and BP cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP, 38.5% (range, 18 to 79) for BP, and 54% (range, 31 to 69) for BV173. CP cells progressively infiltrated BM (21%) and spleen (6%) by 18 to 20 weeks; no animals injected with the cell line or BP cells survived beyond 12 weeks. The rate of increase in human cell numbers was higher for BP (7.3%/week) as compared with CP (0.9%/week) and AP (0. 5%/week). FISH analysis with BCR and ABL probes showed that some of the human cells engrafting after injection of CP cells lacked a BCR-ABL gene and were presumably normal. We conclude that CML cells proliferate in NOD/SCID mice with kinetics that recapitulate the phase of the donor's disease, thus providing an in vivo model of CML biology.
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PMID:The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: an in vivo model of chronic myelogenous leukemia biology. 969 28

The repopulating ability and homing potential of CD34+ cells isolated from either bone marrow (BM) or umbilical cord blood (UCB) was compared in NOD/SCID mice. Mice were sublethally irradiated (3.5 Gy) and within 24 h transplanted i.v. with 10(5)-10(6) CD34+ cells. Four weeks post-transplantation blood was collected from the tail vein for detection of human cells and after 6-7 weeks the mice were sacrificed and blood, BM, thymus, lymph nodes, spleen, liver, lung and kidney were harvested and single cells suspensions were made. Human cells were detected by flow cytometry, and staining was performed for CD34, CD45, and markers of the myeloid, and lymphoid lineages. CD34+ cells from UCB successfully engrafted into the NOD/SCID mice. Eighty-five percent of cells in BM of the mice were of human origin, depending on the dose of cells injected. In all other organs these percentages were always lower, and maximally 63, 13, 3 and 2% in spleen, liver, lung and kidney, respectively. Transplantation of CD34+ cells isolated from human BM, on the other hand, resulted in a very low percentage of human cells after 6-7 weeks of transplantation, not exceeding 3% of the cell suspension. Whether this difference in repopulating ability can be explained by an intrinsic qualitative difference or by differences in quantity of stem cells within the CD34+ compartment from UCB or BM remains to be determined.
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PMID:Comparison of repopulating ability of hematopoietic progenitor cells isolated from human umbilical cord blood or bone marrow cells in NOD/SCID mice. 971 91

Stable gene transfer to human pluripotent hematopoietic stem cells (PHSCs) is an attractive strategy for the curative treatment of many genetic hematologic disorders. In clinical trials, the levels of gene transfer to this cell population have generally been low, reflecting deficiencies in both the vector systems and transduction conditions. In this study, we have used a pseudotyped murine retroviral vector to transduce human CD34(+) cells purified from bone marrow (BM) and umbilical cord blood (CB) under optimized conditions. After transduction, 71% to 97% of the hematopoietic cells were found to express a low-affinity nerve growth factor receptor (LNGFR) marker gene. Six weeks after transplantation into immunodeficient NOD/LtSz-scid/scid (NOD/SCID) mice, LNGFR expression was detected in 6% to 57% of CD45(+) cells in eight of nine engrafted animals. Moreover, proviral DNA was detected in 8.3% to 45% of secondary colonies derived from BM cells of engrafted NOD/SCID mice. Our data show consistent transduction of SCID-repopulating cells (SRCs) and suggest that the efficiency of gene transfer to human hematopoietic repopulating cells can be improved using existing retroviral vector systems and carefully optimized transduction conditions.
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PMID:High efficiency gene transfer to human hematopoietic SCID-repopulating cells under serum-free conditions. 978 52

Purified CD34(+) and CD34(+)CD38(-) human umbilical cord blood (UCB) cells were transduced with the recombinant variant of Moloney murine leukemia virus (MoMLV) MFG-EGFP or with SF-EGFP, in which EGFP expression is driven by a hybrid promoter of the spleen focus-forming virus (SFFV) and the murine embryonic stem cell virus (MESV). Infectious MFG-EGFP virus was produced by an amphotropic virus producer cell line (GP+envAm12). SF-EGFP was produced in the PG13 cell line pseudotyped for the gibbon ape leukemia virus (GaLV) envelope proteins. Using a 2-day growth factor prestimulation, followed by a 2-day, fibronectin fragment CH-296-supported transduction, CD34(+) and CD34(+)CD38(-) UCB subsets were efficiently transduced using either vector. The use of the SF-EGFP/PG13 retroviral packaging cell combination consistently resulted in twofold higher levels of EGFP-expressing cells than the MFG-EGFP/Am12 combination. Transplantation of 10(5) input equivalent transduced CD34(+) or 5 x 10(3) input equivalent CD34(+)CD38(-) UCB cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in median engraftment percentages of 8% and 5%, respectively, which showed that the in vivo repopulating ability of the cells had been retained. In addition, mice engrafted after transplantation of transduced CD34(+) cells using the MFG-EGFP/Am12 or the SF-EGFP/PG13 combination expressed EGFP with median values of 2% and 23% of human CD45(+) cells, respectively, which showed that the NOD/SCID repopulating cells were successfully transduced. EGFP+ cells were found in all human hematopoietic lineages produced in NOD/SCID mice including human progenitors with in vitro clonogenic ability. EGFP-expressing cells were also detected in the human cobblestone area-forming cell (CAFC) assay at 2 to 6 weeks of culture on the murine stromal cell line FBMD-1. During the transduction procedure the absolute numbers of CAFC week 6 increased 5- to 10-fold. The transduction efficiency of this progenitor cell subset was similar to the fraction of EGFP+ human cells in the bone marrow of the NOD/SCID mice transplanted with MFG-EGFP/Am12 or SF-EGFP/PG13 transduced CD34(+) cells, ie, 6% and 27%, respectively. The study thus shows that purified CD34(+) and highly purified CD34(+)CD38(-) UCB cells can be transduced efficiently with preservation of repopulating ability. The SF-EGFP/PG13 vector/packaging cell combination was much more effective in transducing repopulating cells than the MFG-EGFP/Am12 combination.
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PMID:Highly efficient transduction of the green fluorescent protein gene in human umbilical cord blood stem cells capable of cobblestone formation in long-term cultures and multilineage engraftment of immunodeficient mice. 983 3

The use of immunodeficient mice, particularly of the nonobese diabetic/severe combined immunodeficient (NOD/SCID) strain, has allowed detection of very primitive malignant progenitors from patients with acute myelogenous leukemia (AML). To define the sensitivity and reproducibility with which the engraftment of different AML cells can be detected, 61 different samples from patients with newly diagnosed AML representing a variety of cytogenetic and French-American-British (FAB) subtypes were injected into NOD/SCID mice. Eight weeks after intravenous injection of 10(7) AML cells, the average percent of human cells in mouse bone marrow was 13.3%, with 70% of samples showing easily detectable engraftment of CD45(+) cells. AML samples with cytogenetic changes associated with a poor clinical prognosis tended to engraft to higher levels than those with changes associated with a good prognosis. Cells with FAB subtypes M3 and, to a lesser extent, M2, engrafted more poorly (P =.002 and.06, respectively) than those from other subtypes. Intraperitoneal injection of human interleukin-3 and Steel factor thrice weekly for 4 weeks did not enhance the levels of AML cell engraftment. However, AML samples that showed cytokine-independent colony growth in methylcellulose assay or expressed growth-factor mRNA in malignant blasts achieved significantly higher levels of engraftment than those which were cytokine dependent in culture or failed to express cytokine message (P <.03 and P <.02, respectively). In 6 patient samples, the frequency of NOD/SCID leukemia-initiating cells (NOD/SL-IC) varied from 0.7 to 45 per 10(7) cells, which was 200- to 800-fold lower than the frequency of AML long-term culture-initiating cells (AML LTC-IC) in the same samples. Each NOD/SL-IC will produce more than 10(6) leukemic blasts as well as many AML-CFC and AML LTC-IC as detected 8 weeks postinjection into mice. Serial transplant experiments showed the ability of NOD/SL-IC to maintain their own numbers over at least 3 to 4 weeks in vivo. The ability of these progenitors to self-renew combined with their potential to differentiate to produce large numbers of more mature progenitors and leukemic blasts suggests that the NOD/SL-IC assay identifies leukemic 'stem cells' that may maintain the malignant clone in human patients. The further use of this assay should facilitate studies of AML stem cell biology and the evolution of novel therapeutic strategies.
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PMID:Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese diabetic/severe combined immunodeficient mice. 1047 2


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